In healthy young individuals, increasing left-sided filling pressures within the individual's heart is associated with a proportional increase in left ventricular stroke volume; and therefore cardiac output. However, with age, the left ventricle becomes more stiff over time. This process, often accelerated with decades of hypertension or diabetes, results in a failure of increased pressure to increase stroke volume. This pressure-volume relationship is also known as the Frank-Starling curve. Over time, the slope of this curve becomes flat. When this occurs, increasing left-sided filling pressures do not (or do so marginally) improve stroke volume. In some cases, high left-sided filling pressures result in mistral regurgitation and a reduction in cardiac output. As a result, the normal feedback mechanism of increasing blood flow to the heart the body attempts to increase cardiac output (such as during periods of exercise), no longer improves forward flow. Instead, the increased blood flow to the left ventricle results in rising left-sided filling pressures.
Computer modeling has revealed that differences in big-ventricular function are likely more important than total cardiac output in terms of patient symptoms. However discordant the ventricular function may be, the cardiac output of each ventricle must be the same. Therefore, with predominant left heart failure, pressure builds behind the left ventricle. In predominant right heart failure, pressure builds behind the right ventricle. Of importance, exercise/exertion exaggerates differences in ventricular function. Over time and accelerated by disease, most left ventricles develop some degree of diastolic dysfunction. Accordingly, during exercise, the left ventricle cannot “keep up with” the right ventricle. The resulting equilibrium results in rapid elevations in left-sided filling pressures during exercise that limit exercise capacity. An interactive device that can limit the rise in intra-cardiac filling pressures while maintaining cardiac output would dramatically improve exercise capacity and improve patient symptoms of fatigue and shortness of breath.
Long standing elevated left trial (LA) pressure can dilate the left atrium and contribute to trial arrhythmias such as atrial fibrillation. It is likely that increases in ventricular pressures (both right and left ventricular pressures) may result in ventricular arrhythmias as well. By maintaining lower intra-cardiac filling pressures, a system that maintains cardiac output while preventing elevated intra-cardiac pressures may decrease deadly cardiac arrhythmias.
Cardiac output and heart rate have a complicated relationship. Typically, in patients without volume overload, increasing heart rate does not affect cardiac output. This apparent paradox occurs due to a decrease in ventricular filling time and a redistribution of blood from the heart to peripheral tissue. When venous return to the heart is not increased, the stroke volume will fall with increasing heart rate implying an extrathoracic venous collapse. However, in patients that have a more flat pressure-volume relationship, increasing the heart rate can maintain stroke volume and increase cardiac output significantly. The amount of improvement in cardiac output typically depends on the ability of the left ventricle to relax fast enough at higher heart rates. Therefore, optimizing cardiac output is a complex interaction between volume status, heart rate, bi-ventricular pressure-volume curves, and filling parameters.
While increasing cardiac output, increasing heart rate may also increase left-sided filling pressures and exacerbate shortness of breath. Left-sided filling pressures may rise significantly with only marginal improvement in cardiac output. Therefore, the relationships between cardiac output and heart rate in response to changes in left-sided filling pressures and/or changes in heart rate are an important consideration to optimize filling pressures and cardiac output.
Increasing left-sided filling pressures may result in hyperventilation and may contribute to relative bradycardia. Both mechanisms may limit exercise capacity. Animal cork from the 1950's to the early 2000's have identified various receptors that are intimately intertwined with the autonomic nervous system and respiratory function. Increased left-sided filling pressures activate:                1. rapidly adapting receptors (RAR), [Coleridge and Coleridge, 1977b]        2. pulmonary receptors [Ravi and Kappagoda, 1992]        3. bronchial C-fiber receptors [Gunawardena et al., 2002]        4. Slowly adapting stretch receptors [Marshall and Widdicombe, 1958].Therefore, all four types of pulmonary vagal sensory receptors are activated with elevated left-side side filling pressures, which result in increased respiratory rate.        
Preventing increased left-sided filling pressures will therefore improve respiratory rate; and therefore improve exercise capacity in any individual with rising left-sided filling pressures with exercise. Recent human studies have found that even “healthy” individuals, without a diagnosis of heart failure, frequently develop moderate increases in left-sided filling pressures with mild exercise. This device has the potential to improve exercise capacity in these subjects.